Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this study of an antibody to PD-1 demonstrated superior efficacy compared to docetaxel with regard to treatment of advanced, non-squamous cell non-small cell lung cancer.

Be aware that benefits were seen in overall survival as well as progression-free survival.

DENVER -- Patients with previously treated advanced or metastatic squamous non-small cell lung cancer (NSCLC) had improved survival with an immunotherapeutic drug than with chemotherapy, according to updated results from a randomized trial.

Twice as many patients treated with nivolumab (Opdivo) remained alive at 18 months as compared with those treated with docetaxel, and six times as many patients were alive without progression at 18 months with nivolumab as compared with the chemotherapy standard for NSCLC.

"The nivolumab benefit was independent of PD-L1 expression and see across all predefined clinical subgroups," said Reckamp. "The safety profile of nivolumab continues to be favorable versus docetaxel and consistent with prior studies. The majority of patients who developed treatment-related adverse events on nivolumab did so within the first 3 months."

A second trial involving patients with treatment-refractory squamous NSCLC similar improvement in outcomes with nivolumab versus docetaxel.

Accounting for about 20% of NSCLC cases, patients with squamous-cell NSCLC represent a poor-prognosis minority who have few options after progression or failure of first-line platinum-based chemotherapy. Second-line docetaxel is associated with modest clinical activity (median overall survival of 5 to 8 months, objective response rate of 3% to 9%) and significant toxicity.

Nivolumab, a fully human PD-1 immune checkpoint inhibitor antibody, has demonstrated activity in both squamous and nonsquamous NSCLC and received FDA approval earlier this year for patients with squamous NSCLC that had progressed during or after platinum-based chemotherapy.

At the American Society of Clinical Oncology meeting in June, investigators reported preliminary results from a randomized comparison of nivolumab and docetaxel in patients with previously treated advanced/metastatic squamous NSCLC. At that point the data showed a 1-year survival of 42% with nivolumab versus 24% with docetaxel, and a median PFS of 9.2 vs 6.0 months, also in favor of nivolumab.

Reckamp presented updated results from longer follow-up in the trial, known as CheckMate 017. Investigators randomized 272 patients to receive nivolumab or docetaxel, and the primary endpoint was overall survival.

The anti-PD-1 antibody maintained superiority across all prespecified subgroups, including age, geographic location, performance status, and prior therapy. Moreover, the survival benefit persisted across all categories of PD-L1 expression: positive, negative, and not quantifiable.

Similar superiority for nivolumab emerged from the phase II, single-arm CheckMate 063 trial, which involved 117 patients with advanced/metastatic squamous NSCLC that had progressed during or after platinum-based chemotherapy plus at least one other systemic regimen. Two thirds of the patients had received three or more prior regimens, said Leora Horn, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

The trial had a primary endpoint of independently reviewed and confirmed objective response. The data showed an overall response rate of 15% (17 of 117), three fourths of which are ongoing said Horn. The median time to response was 3.3 months, and the median duration of response has yet to be reached (range of 1.9 to 11.5 months). The cohort had a median PFS of 1.9 months and a 1-year PFS of 20%.

Responses were observed across all predefined subgroups, including age, number of prior therapies, performance status, and level of PD-L1 expression.

After a median follow-up of 8 months, the cohort had a median overall survival of 8.1 months, a 1-year overall survival of 39%, and 18-month survival of 27%. The updated data remained consistent with the primary analysis in July 2014, which showed a median overall survival of 8.2 months and 1-year overall survival of 41%.

Overall, 17% of the patients had grade 3/4 adverse events, the most common being gastrointestinal and pulmonary in nature (3% each). Horn noted that no new grade 3/4 adverse events occurred from the initial assessment through the updated analysis in June 2015.